School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham , Nottingham NG7 2RD, U.K.
Cell Signalling Research Group, School of Life Sciences, Queen's Medical Centre, University of Nottingham , Nottingham NG7 2UH, U.K.
J Med Chem. 2018 Feb 8;61(3):1316-1329. doi: 10.1021/acs.jmedchem.7b01811. Epub 2018 Jan 10.
Opioids, like morphine, are the mainstay analgesics for the treatment and control of pain. Despite this, they often exhibit severe side effects that limit dose; patients often become tolerant and dependent on these drugs, which remains a major health concern. The analgesic actions of opioids are primarily mediated via the μ-opioid receptor, a member of the G protein-coupled receptor superfamily. Thus far, development of small molecule fluorescent ligands for this receptor has resulted in antagonists, somewhat limiting the use of these probes. Herein, we describe our work on the development of a small molecule fluorescent probe based on the clinically used opiate morphine and initial characterization of its behavior in cell-based assays.
阿片类药物，如吗啡，是治疗和控制疼痛的主要镇痛药。尽管如此，它们常常表现出严重的副作用，限制了剂量；患者经常对这些药物产生耐受性和依赖性，这仍然是一个主要的健康问题。阿片类药物的镇痛作用主要通过μ-阿片受体介导，μ-阿片受体是 G 蛋白偶联受体超家族的成员。到目前为止，针对该受体的小分子荧光配体的开发导致了拮抗剂的产生，在一定程度上限制了这些探针的使用。在此，我们描述了我们基于临床上使用的鸦片吗啡开发小分子荧光探针的工作以及其在基于细胞的测定中的行为的初步表征。
